January 8, 2007
Nanoparticles Targeted to Brain Tumors
Glioblastoma multiforme is among the most aggressive and difficult cancers to treat. Now, researchers at Penn State University have shown that a lipid-based nanoparticle, designed to bind to a specific receptor found on malignant brain cells but not healthy ones, improves the potency of a common anticancer drug and slows significantly the growth of glioblastoma in mice. The results of these experiments have been published in the journal Molecular Cancer Therapeutics.
James Connor, Ph.D., and colleagues created their new drug delivery vehicle by linking interleukin-13 (IL-13), a molecule produced by the human immune system, to lipid-based nanoparticles coated with poly(ethylene glycol), or PEG. They then used this nanoparticle to encapsulate the anticancer agent doxorubicin. The resulting nanoparticles had an average diameter of approximately 100 nanometers.
Initial experiments showed these nanoparticles did indeed bind to their target on the surface of glioblastoma cells growing in culture and, as a result, were taken up by the cells. In contrast, the nanoparticles did not bind to healthy cells and there was no measurable uptake of these nanoparticles by healthy cells. In another promising finding, the investigators also showed that doxorubicin loaded into these nanoparticles accumulated within drug-resistant tumor cells, which normally pump anticancer agents out from the cell as quickly as the drugs enter.
Based on these results, the investigators treated glioblastoma-bearing mice with doxorubicin loaded into the targeted nanoparticles, doxorubicin loaded into untargeted nanoparticles, or empty targeted nanoparticles. As expected the empty nanoparticles had no effect on tumor growth. In contrast, the drug-loaded, targeted nanoparticles had a marked effect on suppressing tumor growth. After seven weekly injections, tumors in mice dosed with the drug-loaded, targeted nanoparticle were averaged 37 cubic millimeters in volume, compared to 192 cubic millimeters in those animals receiving doxorubicin loaded in untargeted nanoparticles.
This work, which was supported in part by the National Cancer Institute, is detailed in a paper titled, “Interleukin-13 receptor-targeted nanovesicles are a potential therapy for glioblastoma multiforme.” An investigator from the University of Pennsylvania also participated in this study. An abstract of this paper is available through PubMed.